氨酸甲基转移酶G9a和SETD8对质结合性质的DMSO相关影响
Alessandra Feoli1, Giuliana Sarno1,2, Sabrina Castellano1
1Epigenetic Med Chem Lab, Department of Pharmacy, University of Salerno, via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy.
Chembiochem : a European journal of chemical biology
|January 11, 2024
概括
在各种测定中,二甲基硫氧化物 (DMSO) 对蛋白质稳定性和抑制剂结合有不同的影响. 研究人员必须使用正交的生物物理方法,以避免误解药物发现查数据.
科学领域:
- 生物化学 生物化学
- 药物发现 药物发现 药物发现
- 化学生物学 化学生物学
背景情况:
- 甲基二硫氧化物 (DMSO) 是药物发现中的常见溶剂,在测试缓冲器中存在0.1-5% (v/v).
- 即使在低度下,DMSO也可以显著影响蛋白质的行为,并引入实验挑战.
- 了解DMSO的影响对于准确评估候选药物至关重要.
研究的目的:
- 研究DMSO对蛋白质稳定性和抑制剂结合的影响.
- 为了评估DMSO在不同生物物理技术中的影响.
- 强调正交法方法在药物查中的重要性.
主要方法:
- 使用了两个氨酸甲基转移酶:G9a/KMT1C和SETD8/KMT5A.
- 采用纳米差分扫描光测量 (nanoDSF),差分扫描光测量 (DSF),微尺度热泳 (MST) 和表面等离子体共振 (SPR).
- 在不同的DMSO度下评估了蛋白质稳定性和抑制剂结合亲和力.
主要成果:
- DMSO的影响依赖于蛋白质和技术,不能普遍预测.
- 不同的直角生物物理方法为相同的相互作用产生了不同的结合亲和力数据.
- 结果的变化强调需要仔细考虑DMSO的影响.
结论:
- DMSO对蛋白质 - 配体相互作用的影响是复杂的和测试特异性的.
- 采用多个直角生物物理技术对于强大的药物发现查至关重要.
- 在击中化合物选择中的数据解释需要考虑DMSO诱导的变异性.
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